Aza-peptide epoxides: A new class of inhibitors selective for clan CD cysteine proteases

被引:58
作者
Asgian, JL
James, KE
Li, ZZ
Carter, W
Barrett, AJ
Mikolajczyk, J
Salvesen, GS
Powers, JC [1 ]
机构
[1] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA
[2] Babraham Inst, MRC, Mol Enzymol Lab, Cambridge CB2 4AT, England
[3] Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA
关键词
D O I
10.1021/jm025581c
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M-1 s(-1), with the most potent epoxides having the SS stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B.
引用
收藏
页码:4958 / 4960
页数:3
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